scholarly journals Prognostic Markers and Driver Genes and Options for Targeted Therapy in Human-Papillomavirus-Positive Tonsillar and Base-of-Tongue Squamous Cell Carcinoma

Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 910
Author(s):  
Anders Näsman ◽  
Stefan Holzhauser ◽  
Ourania N. Kostopoulou ◽  
Mark Zupancic ◽  
Andreas Ährlund-Richter ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Human Papillomavirus ◽  
Targeted Therapy ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Disease Free Survival ◽  
Tongue Squamous Cell Carcinoma ◽  
Patient Treatment ◽  
Cancer Genes ◽  
Base Of Tongue

The incidence of Human-papillomavirus-positive (HPV+) tonsillar and base-of-tongue squamous cell carcinoma (TSCC and BOTSCC, respectively) is increasing epidemically, but they have better prognosis than equivalent HPV-negative (HPV−) cancers, with roughly 80% vs. 50% 3-year disease-free survival, respectively. The majority of HPV+ TSCC and BOTSCC patients therefore most likely do not require the intensified chemoradiotherapy given today to head and neck cancer patients and would with de-escalated therapy avoid several severe side effects. Moreover, for those with poor prognosis, survival has not improved, so better-tailored alternatives are urgently needed. In line with refined personalized medicine, recent studies have focused on identifying predictive markers and driver cancer genes useful for better stratifying patient treatment as well as for targeted therapy. This review presents some of these endeavors and briefly describes some recent experimental progress and some clinical trials with targeted therapy.

MicroRNA-155, -185 and -193b as biomarkers in human papillomavirus positive and negative tonsillar and base of tongue squamous cell carcinoma

Oral Oncology ◽  
2018 ◽  
Vol 82 ◽  
pp. 8-16 ◽  
Author(s):  
Cinzia Bersani ◽  
Michael Mints ◽  
Nikolaos Tertipis ◽  
Linnea Haeggblom ◽  
Anders Näsman ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Human Papillomavirus ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Tongue Squamous Cell Carcinoma ◽  
Base Of Tongue

scholarly journals Psoriasin expression is associated with survival in patients with human papillomavirus-positive base of tongue squamous cell carcinoma

2021 ◽  
Vol 21 (4) ◽  
Author(s):  
Mark Zupancic ◽  
Linnea Haeggblom ◽  
David Landin ◽  
Linda Marklund ◽  
Tina Dalianis ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Human Papillomavirus ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Tongue Squamous Cell Carcinoma ◽  
Base Of Tongue

Radiotherapy alone or combined with chemotherapy for base of tongue squamous cell carcinoma

2017 ◽  
Vol 127 (7) ◽  
pp. 1589-1594 ◽  
Author(s):  
Kaitlin Christopherson ◽  
Christopher G. Morris ◽  
Jessica M. Kirwan ◽  
Robert J. Amdur ◽  
Peter T. Dziegielewski ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Tongue Squamous Cell Carcinoma ◽  
Base Of Tongue ◽  
Radiotherapy Alone

scholarly journals Tobacco exposure as a major modifier of oncologic outcomes in human papillomavirus (HPV) associated oropharyngeal squamous cell carcinoma

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Hesham Elhalawani ◽  
Abdallah S. R. Mohamed ◽  
Baher Elgohari ◽  
Timothy A. Lin ◽  
Andrew G. Sikora ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Human Papillomavirus ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Cox Regression ◽  
Disease Free Survival ◽  
Oropharyngeal Squamous Cell Carcinoma ◽  
Oncologic Outcomes ◽  
Tobacco Exposure ◽  
Hpv Status

Abstract Background The incidence of oropharyngeal squamous cell carcinoma (OPSCC) in the US is rapidly increasing, driven largely by the epidemic of human papillomavirus (HPV)-mediated OPSCC. Although survival for patients with HPV mediated OPSCC (HPV+ OPSCC) is generally better than that of patients with non-virally mediated OPSCC, this effect is not uniform. We hypothesized that tobacco exposure remains a critical modifier of survival for HPV+ OPSCC patients. Methods We conducted a retrospective analysis of 611 OPSCC patients with concordant p16 and HPV testing treated at a single institute (2002–2013). Survival analysis was performed using Kaplan-Meier analysis and Cox regression. Recursive partitioning analysis (RPA) was used to define tobacco exposure associated with survival (p < 0.05). Results Tobacco exposure impacted overall survival (OS) for HPV+ patients on univariate and multivariate analysis (p = 0.002, p = 0.003 respectively). RPA identified 30 pack-years (PY) as a threshold at which survival became significantly worse in HPV+ patients. OS and disease-free survival (DFS) for HPV+ > 30 PY patients didn’t differ significantly from HPV- patients (p = 0.72, p = 0.27, respectively). HPV+ > 30 PY patients had substantially lower 5-year OS when compared to their ≤30 PYs counterparts: 78.4% vs 91.6%; p = 0.03, 76% vs 88.3%; p = 0.07, and 52.3% vs 74%; p = 0.05, for stages I, II, and III (AJCC 8th Edition Manual), respectively. Conclusions Tobacco exposure can eliminate the survival benefit associated with HPV+ status in OPSCC patients. Until this effect can be clearly quantified using prospective datasets, de-escalation of treatment for HPV + OPSCC smokers should be avoided.

Association of polymorphisms in genes related to cell cycle (ERP29, LEF1, MCC and PTCH1) and DNA transcription factors (IKBKAP and ZNF415) with base of tongue squamous cell carcinoma risk.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 6073-6073
Author(s):  
Carmen Silvia Passos Lima ◽  
Benilton Carvalho ◽  
Renata Pellegrino ◽  
Leticia Khater ◽  
Carlos Takahiro Chone ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Dna Microarrays ◽  
Tongue Squamous Cell Carcinoma ◽  
Nucleotide Polymorphisms ◽  
Dna Transcription ◽  
Base Of Tongue ◽  
First Time

6073 Background: Recently, we found 6.609 genetic single nucleotide polymorphisms (SNPs) with distinct frequencies between base of tongue squamous cell carcinoma (BTSCC) patients and controls. The study was performed using high-resolution DNA microarrays genotyping (Affymetrix). The SNPs identified never have been previously described with BTSCC risk. Some SNPs of interest were located in genes related to cell cycle (ERP29, LEF1, MCC and PTCH1) and DNA transcription (IKBKAP and ZNF415) and they were selected to validation process. Objective: Validate the SNPs ERP29 c.*293A>G (rs7114); LEF1 c.*1213A>G (rs2107028) and g.127267A>G (rs4245926); MCC c.*5077A>G (rs7033); PTCH1 g.27369025G>A (rs16909856) and g.27369324G>A (rs16909859); IKBKAP c.3214T>A (rs3204145) and ZNF415 c.*443A>G (rs3814) associated to BTSCC risk. Methods: Genomic DNA from 49 BTSCC patients and 49 controls was genotyping by TaqMan assays (Applied Biosystems). The differences between groups were analyzed by logistic regression model. Power analysis (PA) was used to verify the effect of sample size on the results obtained. Results: Eight SNPs identified by Affymetrix were validated by TaqMan assays. The frequencies of ERP29 c.*293AG+GG (30 vs 11%, P=0.03; PA=65%), LEF1 c.*1213AA+AG (95 vs 80%, P=0.02; PA=61%) and g.127267AA+AG (93 vs 78%, P=0.02; PA=56%), MCC c.*5077AA+AG (85 vs 64%, P=0.008; PA=67%), PTCH1 g.27369025GG+GA (90 vs 73%, P=0.005; PA=58%) and g.27369324GG+GA (90 vs 73%, P=0.008; PA=58%), IKBKAP c.3214TT+TA (90 vs 72%, P=0.01; PA=62%) and ZNF415 c.*443AA+AG (59 vs 41%, P=0.02; PA=43%) were more common in patients than in controls. Individuals with these genotypes were at 2.9(CI95%: 1.1-8.4), 3.9 (CI95%: 1.4-11.2), 4.0 (CI95%: 1.2-14.7), 3.5 (CI95%: 1.2-11.9), 5.0 (CI95%: 1.7-16.9), 4.5 (CI95%: 1.5-15.2), 4.1 (CI95%: 1.4-12.9), and 3.9 (CI95%: 1.2-13.7)-fold increased risks for BTSCC than others, respectively. Conclusions: Our data present for the first time evidence that inherited abnormalities in ERP29, MCC, LEF1, PTCH1, IKBKAP, and ZNF415 genes may be important determinants of BTSCC. Financial support: FAPESP and FINEP.

scholarly journals Targeted Therapy With PI3K and FGFR Inhibitors on Human Papillomavirus Positive and Negative Tonsillar and Base of Tongue Cancer Lines With and Without Corresponding Mutations

2021 ◽  
Vol 11 ◽  
Author(s):  
Stefan Holzhauser ◽  
Nicole Wild ◽  
Mark Zupancic ◽  
Ramona G. Ursu ◽  
Cinzia Bersani ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Human Papillomavirus ◽  
Targeted Therapy ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Squamous Cell ◽  
Approved Drugs ◽  
Dose Dependent ◽  
Fda Approved Drugs ◽  
Fgfr3 Mutations

ObjectivesHuman papillomavirus positive (HPV+) tonsillar and base of tongue squamous cell carcinoma (TSCC/BOTSCC), the major subsites of oropharyngeal squamous cell carcinoma (OPSCC) have favorable outcome, but upon relapse, outcome is poor and new therapies needed. Since, phosphatidyl-inositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) and fibroblast-growth-factor-receptor-3 (FGFR3) mutations often occur in such tumors, here, we tested targeted therapy directed to such genes in TSCC/BOTSCC cell lines. We also combined the two types of inhibitors with each other, and cisplatin or docetaxel that are used clinically.MethodsThe HPV+ CU-OP-2, -3, -20, UPCI-SCC-154, and HPV- CU-OP-17 and UT-SCC-60A cell lines were first tested for common PIK3CA/FGFR3 mutations by competitive-allele-specific TaqMan-PCR. They were then treated with the food and drug administration (FDA) approved drugs, alpelisib (BYL719) and erdafitinib (JNJ-42756493) alone and in combination with cisplatin or docetaxel. Viability, proliferation, apoptosis and cytotoxicity responses were thereafter followed by WST-1 assays and the IncuCyte S3 Live® Cell Analysis System.ResultsHPV+ CU-OP-2 had a pS249C-FGFR3, and like CU-OP-20, a pE545K-PIK3CA mutation, while no other lines had such mutations. Irrespectively, dose dependent responses to all PI3K/FGFR inhibitors were obtained, and upon combining the inhibitors, positive effects were observed. Cisplatin and docetaxel also induced dose dependent responses, and upon combination with the inhibitors, both positive and neutral effects were found.ConclusionsThe data suggest that FDA approved drugs alpelisib and erdafitinib efficiently inhibit TSCC/BOTSCC cell line growth, especially when combined irrespective of presence of corresponding mutations and should be further explored, for use upon recurrent disease.

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